The prevalence of adolescent obesity is high in the U.S., and in Latin America. While dramatic environmental changes in the food and physical environment are associated with increased risk, there continues to be inadequate understanding of the individual, family and community level factors that protect against the development of obesity. Further research is needed to understand the mechanisms leading to disparate risk for obesity in low-income and Hispanic/Latino youth. The proposed 5-year project aims to elucidate interconnected biological and social pathways associated with adolescent obesity and risk for later development of type 2 diabetes and cardiovascular disease. This application involves approximately 620 Chilean adolescents, assessed in infancy, 3 to 5 years and 10 years as part of a NIH-supported cohort study of the behavioral and developmental effects of preventing iron deficiency anemia in infancy (n = 1645). As such, detailed longitudinal data related to growth, health and development have been collected. At 16 to 17 years, the youth will participate in study of activity, sleep and eating patterns using actigraphic recording and laboratory assessment of eating behavior. In addition, we will measure anthropometry, fat and muscle mass (DXA), fasting glucose, insulin (HOMA IR), lipids, leptin, ghrelin, adiponectin, orexin, CRP, and TNF alpha. Detailed information about family history, smoking, health, and psychosocial functioning will also be collected. Neighborhood level factors such as crime, walk ability and resources for physical activity and healthful food attributes will be assessed. Furthermore, a sizeable subset (n = 237) with sleep neurophysiology and actigraphic recordings at multiple time points will participate in 2-night polysmnographic sleep study at 16 years. Guided by a life-course approach, we propose to investigate three Specific Aims: Specific Aim 1 - To evaluate biological and psychosocial determinants of obesity and related metabolic disturbance in a cohort of adolescents followed since early infancy. Specific Aim 2 - To assess associations between obesity/adiposity and biomarkers of adiposity-related metabolic disturbance in this sample of Chilean adolescents. Specific Aim 3 - To assess the role of circadian patterns of physical activity, sleep and eating behavior on adiposity and related metabolic disturbance. The long standing collaboration between the Institute for Nutrition and Technology at the University of Chile and the Center for Human Growth and Development at the University of Michigan provides an outstanding environment to study biological and psychosocial determinants of adolescent obesity in a low- to middle-income cohort of Latin American youth who are very similar in obesity risk to comparable U.S. youth. We expect to advance understanding of how developmental patterns of eating and activity are influenced by early life factors and in turn influence the development of obesity and related metabolic disturbance. Our study is unique in the depth and breadth of longitudinal psychosocial and biological data. We propose research that crosses disciplinary boundaries and has the potential to reveal important determinants of adolescent obesity for future intervention research.